The present invention relates generally to powder dispenser assemblies, and more particularly, is directed to a powder dispenser assembly used for inhalation of a metered dose of a powdered medicament.
When delivering medicaments, that is, pharmacologically active compounds in solid, micronized form, to the respiratory tract and to the lungs, careful attention to the accuracy of the dosage must be made, which can be as small as 0.1 mg. This is because such medicaments are often quite potent, and the administration of excessive amounts thereof could cause damage to the respiratory tract and to the lungs. In like manner, if the dosage that is delivered is too small, it will not serve its purpose.
It is also necessary that the particles that leave the dispenser assembly be within a particular range, since particles of the medicament which are too large may not enter the respiratory tract, but instead, will be deposited in the mouth and thence to the digestive tract. As an example, the particles can have a diameter of 5 .mu.m or less.
Various devices have been used in order to dispense a metered dose of powdered medicament, including pressurized aerosol devices, nebulizing devices, pump inhalators and the like. With the concern over environmental issues, however, aerosol devices, which constitute a large part of the devices now on the market, are being shunned. Further, with aerosol devices, the medicament is dissolved or suspended in a liquid propellant mixture, and this further adds to the complexity of the devices.
In addition to the aforementioned types of dispenser assemblies, powder dispenser assemblies are also known. Studies have shown that there are virtually no significant differences in bronchodilator responses to medicinal substances administered either by powder dispensing devices or aerosol devices. Accordingly, there is now an ever-growing demand for powder dispensing devices which can dispense metered doses of powdered medicament. With such devices, the powder is dispensed with the start of inspiration following expiration so that there is no need to provide a synchronized release of medication with the start of inspiration to insure quality of the product under this use.
For example, U.S. Pat. No. 4,274,403 to Struve discloses an inhaler including a body having a dispensing head coupled thereto. The body includes a first storage chamber for storing a supply of powdered drugs therein and a second storage chamber for holding a desiccating agent. A dispensing cylinder is contained in a transverse bore in the dispensing head and is laterally movable from a first transverse position in which a diametrical bore is in alignment with a feed hole of the first storage chamber and a second transverse position in which the diametrical bore is out of alignment with the first storage chamber and communicates with the dispensing passageway of the nozzle of the dispensing head. In operation, the user inverts the inhaler such that the first storage chamber is positioned above the diametrical bore. In this position, the powdered drug therein falls into the diametrical bore and remains therein. Then, the user depresses the head of the dispensing cylinder against the action of a spring so as to move the diametrical bore out of alignment with the feed hole for the first storage chamber and into alignment with the dispensing passageway of the nozzle. The inhaler is then inverted back to the position in which the first storage chamber is positioned below the dispensing head, and the nozzle thereof is inserted in a nostril of the user so that upon inhalation, the powdered drug in the diametrical bore is nasally inhaled. To aid in such inhalation, a horizontally extending bore connects the diametrical bore or metering chamber to ambient atmosphere in the second transverse position.
However, in normal use, it is required that the inhaler be inverted so that the first storage chamber is above the dispensing head in order to dispense the powdered drug therefrom into the diametrical bore metering chamber, and then the inhaler must be reinverted to its original position in which the first storage chamber is below the dispensing head for the inhalation process. This becomes cumbersome in practice. In addition, the use of a dispensing cylinder having a single diametrical bore therein as the metering chamber is disadvantageous. This is because a single elongated diametrical bore of reduced cross-section provides some resistance to inhalation, particularly when the device is used by those persons having difficulty breathing and who cannot therefore provide the necessary suction. In addition, the use of such single diametrical bore with the air passageway extending substantially midway therein, may result in the powdered drug in the diametrical bore metering chamber, which is at a level below the intersection with the air passageway, remaining in the diametrical bore. As a result, the user may not inhale the entire metered amount in the diametrical bore metering chamber.
U.K. Patent No. 2,165,159 to Auvinent et al. discloses a dosing device having a fixed storage chamber for a medicinal powder, a mouthpiece and a venturi restriction between the mouthpiece and the storage chamber. A metering device is provided in the housing between the venturi restriction and the storage chamber and includes a rod having depressions therein for measuring the dose of the medicinal substance. The rod is rotatable to thereby deposit the medicinal powder in a depression thereof to the venture restriction. The device for rotating the rod is an indexing mechanism much like that of a ball-point pen. However, because of the cup-like arrangement of this patent, adhesion can occur along the walls of each depression, which is disadvantageous from a delivery viewpoint. See also European Patent Application No. 0079478 for a similar disclosure.
U.K. Patent No. 2,041,763 to Chiesi et al., the entire disclosure of which is incorporated herein by reference, discloses an inhaler for pulverulent medicinal substances, in which there is rotation of the housing parts relative to each other in order to obtain proper dosing and dispensing for inhalation through the nozzle. Specifically, there is a rotatable arrangement with the nozzle, the conduit connected to the nozzle and the storage chamber adjacent the conduit for storing an active compound to be dispensed by the inhalator. The bottom of the body which defines the storage chamber has two opposing arcuate dosing holes, each of which has a volume exactly corresponding to one dose of medicament. The tubular element which forms the conduit has a skirt corresponding to the length of the dosing holes for closing the dosing holes alternatively. Further, a dispensing disk provided with a dispensing hole is positioned immediately below the bottom such that the hole can be provided in registration with either of the dosing holes. The dispensing disk is secured to the bottom of the element which defines the conduit. In this regard, the skirt, conduit and dispensing disk move together as a unit in relation to the bottom containing the dosing holes. Immediately below the dispensing disk, there is provided a cavity communicating with the bottom of the conduit.
However, there is no dosing loading means for introducing the active compound from the storage chamber through the dosing holes. Rather, the medicament falls by gravity into the dosing holes. Accordingly, the device may not be suitable for use with micronized powder which requires dosage accuracy, since the micronized medicament will not fall by its own weight with any predictable accuracy into or out of the dosing holes, but rather, will stick together and stick to the walls of the chamber. Further, neither of the dosing holes is positioned across the conduit at any time. Rather, the dosing holes are always in surrounding relation to the conduit. As a result, the air flow to the user is somewhat tortuous, and some of the medicament may not be removed, causing dosage inaccuracy.
U.S. Pat. No. 4,524,769 to Wetterlin, the entire disclosure of which is incorporated herein by reference, attempts to cure the deficiencies of Chiesi et al. Specifically, this patent to Wetterlin, which is similar in many respects to Chiesi et al., includes a dosing unit that includes a storage chamber for holding the active compound, a perforated membrane rotatably positioned under the storage chamber and a holder for the membrane. Introduction of the active compound into the perforations in the perforated membrane is accomplished with elastic, spring-loaded scrapers, mounted in a holder in the storage chamber. With this arrangement, the membrane is movable between a first position where active compound is introduced by the scrapers in part of the area of the perforated membrane, and a second position where the part area of the loaded membrane has been inserted into the air conduit in the dosage inhalator. Thus, the active compound contained in the perforations is entrained at inhalation and brought through the nozzle to the respiratory tract and the lungs of the patient.
However, with this arrangement, a separate coil spring must be used to bias the scrapers into engagement with the perforated membrane, thereby complicating the construction and assembly of the device. The coil spring is interposed in the storage chamber between the casing and the scraper assembly. Alternatively, it is disclosed that the separate coil spring can be arranged so that the membrane is pressed against the scrapers, and thereby mounted in the base or maneuvering unit. In addition to the coil spring, Wetterlin uses spring loaded pins beneath the membrane to engage the ratcheted bottom of the membrane in order to provide distinct positions for the perforated membrane when it is advanced by the base or maneuvering unit. This, of course, further complicates the construction and assembly of the device. See also U.S. Pat. Nos. 4,907,583; 4,534,345; and 4,667,668, all to Wetterlin.
Other patents of related interest are U.S. Pat. No. 2,581,182 to Fields, European Patent Application No. 0079478 to Douglas, U.S. Pat. No. 4,046,146 to Rosskamp et al., U.S. Pat. No. 4,627,432 to Newell et al. and U.S. Pat. No. 4,811,731 to Newell et al.